Moghadam Nahid, Xiao Yong, Dragon Francois, Barbeau Benoit
Department of Biological Sciences, University of Quebec at Montreal (UQAM), 141 President-Kennedy Avenue, Montreal, QC H2X 3X8, Canada.
Centre d'Excellence en Recherche sur les Maladies Orphelines-Fondation Courtois, 141 President-Kennedy Avenue, Montréal, QC H2X 3X8, Canada.
Viruses. 2025 May 19;17(5):727. doi: 10.3390/v17050727.
Human T cell leukemia virus type 1 (HTLV 1) is an oncogenic retrovirus responsible for the development of adult T cell leukemia (ATL). The minus strand of HTLV-1 provirus encodes an oncoprotein named HTLV-1 bZIP factor (HBZ), which plays a pivotal role in viral replication and T cell proliferation. Of particular interest is the spliced HBZ isoform (sHBZ), which is predominantly expressed in ATL cells and localizes within the nucleolus, conferring immortalizing properties to T cells. Our previous study has shown that sHBZ colocalizes and associates with Nucleophosmin/B23, a nucleolar phosphoprotein with multiple functions. In this study, through an optimized nucleolar isolation method, we first confirmed sHBZ's nucleolar localization via Western blotting in transfected HEK293T cells, chronically HTLV-1-infected T cell lines, and freshly infected HeLa cells. We further demonstrated that the sHBZ/B23 association predominantly occurs in the nucleolus by co-immunoprecipitation of cell fractions. Our study highlights the nucleolar localization of sHBZ and its possibly essential interaction with this nucleolar-residing protein, leading to cell immortalization.
人类T细胞白血病病毒1型(HTLV-1)是一种致癌逆转录病毒,可导致成人T细胞白血病(ATL)的发生。HTLV-1前病毒的负链编码一种名为HTLV-1 bZIP因子(HBZ)的癌蛋白,它在病毒复制和T细胞增殖中起关键作用。特别值得关注的是剪接后的HBZ异构体(sHBZ),它主要在ATL细胞中表达,并定位于核仁,赋予T细胞永生特性。我们之前的研究表明,sHBZ与核仁磷酸蛋白Nucleophosmin/B23共定位并相互作用,Nucleophosmin/B23具有多种功能。在本研究中,通过优化的核仁分离方法,我们首先通过蛋白质免疫印迹法在转染的HEK293T细胞、长期感染HTLV-1的T细胞系和新感染的HeLa细胞中证实了sHBZ的核仁定位。我们进一步通过细胞组分的免疫共沉淀证明,sHBZ与B23的相互作用主要发生在核仁中。我们的研究突出了sHBZ的核仁定位及其与这种核仁驻留蛋白可能的重要相互作用,从而导致细胞永生化。